Prevention of Pegfilgrastim-Induced Bone Pain: A Phase III Double-Blind Placebo-Controlled Randomized Clinical Trial of the University of Rochester Cancer Center Clinical Community Oncology Program Research Base
Pegfilgrastim-induced bone pain is a significant clinical problem that may result in discontinuation of pegfilgrastim and lead to less effective chemotherapy dosing. Interventions for pegfilgrastim-induced bone pain are needed.
The University of Rochester Cancer Center Clinical Community Oncology Program Research Base randomly assigned 510 patients at 17 sites to receive either naproxen (500 mg two times per day) or placebo on the day of pegfilgrastim administration, continuing for 5 to 8 days after pegfilgrastim. Patients recorded pain severity (using a scale of 0 to 10) and duration in daily diaries. The primary outcome measure was the area under the curve (AUC) for pain for days 1 through 5. Secondary outcome measures included the identification of risk factors for the development of pain and response to naproxen.
Patients' mean age was 55.6 years and 86% were female. Sixty-eight percent of patients had breast cancer and 10% had lung cancer. Pain reached its peak at 3 days for both groups. The mean AUC for pain was 7.71 for the placebo group and 6.04 for the naproxen group (P = .037). Naproxen reduced maximum pain from 3.40 to 2.59 (P = .005). Naproxen also reduced overall pain incidence from 71.3% to 61.1% (P = .020) and duration from 2.40 to 1.92 days (P = .009). The reduction in severe pain (> 5 on a scale of 1 to 10) from 27.0% to 19.2% was also significant (P = .048). Risk factors could not be identified to predict incidence, severity, or ability to prevent pegfilgrastim-induced bone pain.
Our phase III randomized placebo-controlled clinical trial demonstrated that naproxen at a dose of 500 mg twice per day is effective in reducing the incidence and severity of pegfilgrastim-induced bone pain.
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"Although there are reports of chemotherapy-induced bone pain and leg weakness  , it remains unclear whether and how MTX chemotherapy directly causes bone pain. Sensation (nociception) of bone pain is resulted from the stimulation of both myelinated and unmyelinated primary sensory neurons (nociceptors) in the dorsal root ganglia (DRGs). "
[Show abstract][Hide abstract]ABSTRACT: Granulocyte-colony stimulating factors (G-CSFs) are commonly employed in clinical practice. The most relevant adverse event of G-CSF administration is bone pain. Approximately 20% of cancer patients experienced bone pain with the administration of prophylactic daily G-CSFs (lenograstim and filgrastim). The reported incidence of bone pain in cancer patients undergoing pegfilgrastim prophylaxis ranged from 25% to 38%. In healthy donors the incidence of bone pain was higher than in cancer patients, ranging from 52% to 84%. There are four main causes of G-CSF related bone pain: bone marrow quantitative and qualitative expansion, peripheral nociceptor sensitization to nociceptive stimuli, modulation of immune function and direct effect on bone metabolism. For the prevention and treatment of bone pain occurring after or during GCSFs administration, acetaminophen and nonsteroidal anti-inflammatory agents are commonly used as first-line treatment; antihistamines, opioids and dose reduction of G-CSFs are considered as second line therapy. The only randomized clinical trial conducted for the prevention and treatment of G-CSF induced bone pain showed the efficacy of naproxen in reducing the incidence, the severity and the duration of bone pain induced by the administration of pegfilgrastim.
Full-text · Article · Aug 2013 · Critical reviews in oncology/hematology